Pre-treatment with the mGlu2/3 receptor agonist LY379268 attenuates DOI-induced impulsive responding and regional c-Fos protein expression

Abstract

Our results suggest that impulsivity is possibly due to a primary increase in Glu transmission mediated via 5-HT(2A) receptor activation. Thus, mGlu2/3 receptor agonists might have some potential for treating motor impulsivity-related impairments while their cognitive enhancing effects were not confirmed in this study.

Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

“…68 We propose that vulnerability to motor impulsivity associates with expression patterns of 5-HT 2A R and 5-HT 2C R (present study), 6,7,9 while multiple studies implicate dopamine 5,7,69 , γ-aminobutyric acid (GABA) 8,10 and glutamate system involvement. 37,70–73 Our observation that knockdown of the mPFC 5-HT 2C R does not fully recapitulate the motor impulsivity phenotype characterized in outbred rats suggests an interplay between serotonergic and other neurochemical circuits may be differentially recruited in the expression of distinct components of impulsive behavior. One candidate mechanism is the interaction between 5-HT and glutamate systems in the mPFC.…”

Activation of Adenosine1 Receptors Induces Antidepressant-Like, Anti-Impulsive Effects on Differential Reinforcement of Low-Rate 72-s Behavior in Rats

“…Alterations of motoric impulsivity (behavioral inhibition) may be a shared explanatory construct (Pattij et al, 2003;Navarra et al, 2008;Robinson et al, 2008) for these drugs and a range of other drugs including tricyclic antidepressants and norepinephrine transporter inhibitors (Winstanley et al, 2004;Greco et al, 2005;Carli et al, 2006;Blondeau and DelluHagedorn, 2007;Paine et al, 2007;Wischhof and Koch, 2012). This potential involvement of impulsivity in mediating the antidepressant-like effects of norepinephrine transporter inhibitors, tricyclic antidepressants, 5-HT 2A receptor antagonists, mGlu 2 receptor PAMs, and adenosine A 1 receptor agonists on DRL behavior highlights an important differential feature compared with the FST, for which adenosine A 1 receptor agonists and mGlu2 receptor agonists also test similarly to antidepressants.…”

“…The similar distribution of mGlu 2 and adenosine A 1 receptors throughout the limbic forebrain probably is an important underpinning to similar effects of activating these receptors across a wide range of neuropsychiatric preclinical models (Bauer et al, 2003;Richards et al, 2005). Hallucinogen-induced head shakes and hallucinogen/ (5S,10R)-(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine (MK-801)-induced immediate early gene expression are modulated by mGlu 2 or adenosine A 1 receptors in the PFC or on thalamocortical pathways (Scruggs et al, 2000;Gotoh et al, 2002;Pei et al, 2004;Benneyworth et al, 2007;Marek, 2009;Wischhof and Koch, 2012). Although adenosine A 1 receptors are located at both postsynaptic and presynaptic sites, these receptors are known to play a prominent role as heteroreceptors, decreasing excitatory amino acid release, similar to the mGlu 2 receptor role as an autoreceptor.…”

Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System

“…Several studies have demonstrated that systemic administration of the preferential 5-HT 2A R agonist DOI elicits modest increases in premature responses in the 5-CSRT task (Koskinen et al, 2000a(Koskinen et al, , b, 2003Koskinen and Sirvio, 2001;Wischhof and Koch, 2012). Given the observation that the DOI-induced head-twitch response pharmacologically dissociated HI and LI rats (Figure 2a), we next sought to Figure 2 Inherent impulsive action predicts the DOI-elicited head-twitch response.…”